The unfolded protein response is required for dendrite morphogenesis

  1. Xing Wei
  2. Audrey S Howell
  3. Xintong Dong
  4. Caitlin A Taylor
  5. Roshni C Cooper
  6. Jianqi Zhang
  7. Wei Zou
  8. David R Sherwood
  9. Kang Shen  Is a corresponding author
  1. Howard Hughes Medical Institute, Stanford University, United States
  2. University of Southern California, United Kingdom
  3. Duke University, United States

Abstract

Precise patterning of dendritic fields is essential for the formation and function of neuronal circuits. During development, dendrites acquire their morphology by exuberant branching. How neurons cope with the increased load of protein production required for this rapid growth is poorly understood. Here we show that the physiological unfolded protein response (UPR) is induced in the highly branched Caenorhabditis elegans sensory neuron PVD during dendrite morphogenesis. Perturbation of the IRE1 arm of the UPR pathway causes loss of dendritic branches, a phenotype that can be rescued by overexpression of the ER chaperone HSP-4 (a homologue of mammalian BiP/ grp78). Surprisingly, a single transmembrane leucine-rich repeat (LRR) protein, DMA-1, plays a major role in the induction of the UPR and the dendritic phenotype in the UPR mutants. These findings reveal a significant role for the physiological UPR in the maintenance of ER homeostasis during morphogenesis of large dendritic arbors.

Article and author information

Author details

  1. Xing Wei

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  2. Audrey S Howell

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  3. Xintong Dong

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  4. Caitlin A Taylor

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. Roshni C Cooper

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  6. Jianqi Zhang

    Division of Biostatistics, Department of Preventive Medicine, University of Southern California, Los Angeles, United Kingdom
    Competing interests
    No competing interests declared.
  7. Wei Zou

    Department of Biology, Duke University, Durham, United States
    Competing interests
    No competing interests declared.
  8. David R Sherwood

    Department of Biology, Duke University, Durham, United States
    Competing interests
    No competing interests declared.
  9. Kang Shen

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    For correspondence
    kangshen@stanford.edu
    Competing interests
    Kang Shen, Reviewing editor, eLife.

Copyright

© 2015, Wei et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 3,470
    views
  • 866
    downloads
  • 43
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Xing Wei
  2. Audrey S Howell
  3. Xintong Dong
  4. Caitlin A Taylor
  5. Roshni C Cooper
  6. Jianqi Zhang
  7. Wei Zou
  8. David R Sherwood
  9. Kang Shen
(2015)
The unfolded protein response is required for dendrite morphogenesis
eLife 4:e06963.
https://doi.org/10.7554/eLife.06963

Share this article

https://doi.org/10.7554/eLife.06963

Further reading

    1. Cell Biology
    2. Developmental Biology
    Deepak Adhikari, John Carroll
    Insight

    The formation of large endolysosomal structures in unfertilized eggs ensures that lysosomes remain dormant before fertilization, and then shift into clean-up mode after the egg-to-embryo transition.

    1. Cell Biology
    2. Developmental Biology
    Filip Knop, Apolena Zounarová ... Marie Macůrková
    Research Article Updated

    During Caenorhabditis elegans development, multiple cells migrate long distances or extend processes to reach their final position and/or attain proper shape. The Wnt signalling pathway stands out as one of the major coordinators of cell migration or cell outgrowth along the anterior-posterior body axis. The outcome of Wnt signalling is fine-tuned by various mechanisms including endocytosis. In this study, we show that SEL-5, the C. elegans orthologue of mammalian AP2-associated kinase AAK1, acts together with the retromer complex as a positive regulator of EGL-20/Wnt signalling during the migration of QL neuroblast daughter cells. At the same time, SEL-5 in cooperation with the retromer complex is also required during excretory canal cell outgrowth. Importantly, SEL-5 kinase activity is not required for its role in neuronal migration or excretory cell outgrowth, and neither of these processes is dependent on DPY-23/AP2M1 phosphorylation. We further establish that the Wnt proteins CWN-1 and CWN-2, together with the Frizzled receptor CFZ-2, positively regulate excretory cell outgrowth, while LIN-44/Wnt and LIN-17/Frizzled together generate a stop signal inhibiting its extension.